This research is designed to investigate the role played by drug receptor sites in regulating the proliferation and differentiation of the hemopoietic stem cell. The study seeks to uncover receptor sites that switch DNA synthesis on or off in hemopoietic cells. Any role played by drug receptors in the leukemogenic process (i.e., during the spontaneous development of leukemia) or in adverse effects on bone marrow of clinically useful drugs will be studied. The phosphodiesterase enzymes vary in their sensitivity to a particular inhibitor. By investigating a variety of agents that inhibit phosphodiesterases an attempt will be made to manipulate the cell cycle in tissues such as bone marrow. Such manipulation of the cell cycle may be a means of altering the sensitivity of tissues to cycle-dependent anticancer agents or cycle-dependent drugs used in immunosuppressive treatment. Hence, attempts will be made to promote a more selective action of cytotoxic drugs on specific tissues. It is not known whether drug receptors play a direct role in the antiproliferative action of cytotoxic agents. Studies will be designed to determine whether previous blocking of receptor sites (without alteration of the cell cycle state) would modify the cell-killing action of such compounds. By interchanging drug-receptor blocking compounds, the complexity of receptor mechanisms that initiate the GO yields S-phase transition of the bone marrow stem cell will be studied. It may be possible, therefore, to determine whether single receptors or a multiple of qualitatively different receptors interact to induce cell cycle changes.